Chemical signal-impermeable mask

ABSTRACT

A chemical signal-impermeable mask is positioned in the electrolyte flow such that the mask is between a source of chemical signal and a working electrode which senses the chemical signal transported from the source (e.g., by diffusion). The configuration of the mask is such that the mask prevents substantially all chemical signal transport from the chemical signal source having a radial vector component relative to a plane of the mask and the catalytic face of the working electrode, thus allowing primarily only chemical signal transport that is substantially perpendicular to the place of the mask and the catalytic surface of the working electrode. By reducing or eliminating chemical signal radial transport toward the working electrode, the mask thus significantly reduces or eliminates edge effects. By substantially reducing edge effects created by radial transport of chemical signal, it is possible to obtain a more accurate measurement of the amount (e.g., concentration) of chemical signal that is transported from a given area of source material.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation U.S. application Ser. No. 08/959,599,filed Oct. 29, 1997, now U.S. Pat. No. 5,827,183 currently pending,which is a divisional of U.S. application Ser. No. 08/527,061, filedSep. 12, 1995, now U.S. Pat. No. 5,735,273, from which applicationspriority is claimed pursuant to 35 U.S.C. §120 and which areincorporated herein by reference in their entirety.

FIELD OF THE INVENTION

This invention relates generally to the detection of chemical signalsthat are diffused through a solid or semi-solid, or quiescent liquidsurface, particularly where the chemical signals are associated with amedically important molecule.

BACKGROUND OF THE INVENTION

An electrode is the component in the electrochemical cell in contactwith an electrolyte through which current can flow by electronicmovement. Electrodes, which are essential components of both galvanic(current producing) and electrolytic (current using) cells, can becomposed of a number of electrically conductive materials, e.g., lead,zinc, aluminum, copper, iron, nickel, mercury, graphite, gold, orplatinum. Examples of electrodes are found in electric cells, where theyare dipped in the electrolyte; in medical devices, where the electrodeis used to detect electrical impulses emitted by the heart or the brain;and in semiconductor devices, where they perform one or more of thefunctions of emitting, collecting, or controlling the movements ofelectrons and ions.

The electrolyte can be any substance that provides ionic conductivity,and through which electrochemically active species can be transported(e.g., by diffusion). Electrolytes can be solid, liquid, or semi-solid(e.g., in the form of a gel). Common electrolytes include sulfuric acidand sodium chloride, which ionize in solution. Electrolytes used in themedical field must have a pH which is sufficiently close to that of thetissue in contact with the electrode (e.g., skin) so as not to causeharm to the tissue over time.

Electrochemically active species that are present in the electrolyte canundergo electrochemical reactions (oxidation or reduction) at thesurface of the electrode. The rate at which the electrochemicalreactions take place is related to the reactivity of the species, theelectrode material, the electrical potential applied to the electrode,and the efficiency at which the electrochemically active species istransported to the electrode surface.

In unstirred electrolyte, such as quiescent liquid solutions and gelelectrolytes, diffusion is the main process of transport ofelectrochemically active species to the electrode surface. The exactnature of the diffusion process is determined by the geometry of theelectrode (e.g., planar disk, cylindrical, or spherical), and thegeometry of the electrolyte (e.g., semi-infinite large volume, thin diskof gel, etc.). For example, diffusion of electrochemically activespecies to a spherical electrode in a semi-infinite volume ofelectrolyte differs from diffusion of electrochemically active speciesto a planar disk electrode. A constant and predictable pattern ofdiffusion (i.e., a diffusion pattern that can be predicted by a simpleequation) is critical in determining a correlation between theelectrochemical current collected, and the concentration of theelectrochemically active species in the electrolyte.

However, diffusion of electrochemically active species toward anelectrode can not be predicted by a simple equation for every situation.For example, where the electrochemically active species diffuses througha disk-shaped electrolyte toward a smaller disk-shaped electrode incontact with the electrolyte, the current observed at the electrode cannot be predicted by a simple equation. In this latter situation, theinaccuracy in the diffusion model is caused by the combination of twodifferent diffusion models. First, in the center of the disk electrodethe diffusion of the electroactive species towards the electrode is in asubstantially perpendicular direction. Secondly, at the edges of thedisk electrode the diffusion comes from both perpendicular and radialdirections. The combination of these two different diffusion patternsmakes the total current collected at the disk electrode difficult topredict. In addition, the relative contributions of the diffusion fluxesfrom the axial and radial directions may change over time, causingfurther errors in predicted current.

SUMMARY OF THE INVENTION

A mask which is substantially impermeable to the transport of a chemicalsignal is positioned in the chemical signal transport path moving towarda working electrode which senses an electrochemical signal diffusedthrough a material which is ionically conductive, which materialcomprises water and an electrolyte. More particularly, the mask of theinvention is positioned on or in the ionically conductive material, suchas an ion-containing gel, between an area from which the chemical signalis transported and the catalytic face of the working electrode used tosense the chemical signal. The configuration of the mask (e.g., shape,thickness, mask component(s)) is such that the mask preventssubstantially all chemical signal transport (from the chemical signalsource) having a radial vector component relative to a plane of the maskand the catalytic face of the working electrode, thus allowing primarilyonly chemical signal transport (e.g., diffusion) that is substantiallyperpendicular to the place of the mask and the catalytic surface of theworking electrode. The mask thus minimizes radial transport of thechemical signal to the working electrode and accumulation of chemicalsignal at the periphery of the working electrode. The mask thussignificantly reduces or eliminates edge effects, since the chemicalsignal that reaches the electrode is primarily only that chemical signalthat is transported in a direction substantially perpendicular to thecatalytic face of the working electrode. Substantially all transport ofchemical signal to the working electrode surface via a path whichincludes an radial vector component (i.e., is not a path substantiallyperpendicular to the working electrode catalytic surface) is preventedfrom occurring by the mask, since the mask blocks entry of potentiallyradially transported chemical signal at the source. By substantiallyreducing edge effects created by radial transport of chemical signal, itis possible to obtain a more accurate measurement of the amount (e.g.,concentration) of chemical signal that is transported from a given areaof source material.

In one embodiment, the working electrode is a closed polygon or closedcircle. The mask has an outer perimeter which is equal to or greaterthan (i.e., extends beyond) the outer perimeter of the workingelectrode. The mask has an opening, the opening being sufficiently smallso that chemical signal that passes through the opening to the catalyticsurface of the working electrode in a direction that is substantiallyperpendicular to the plane of the mask, and thus, substantiallyperpendicular to the working electrode catalytic face.

In another embodiment, the working electrode is annular and the mask iscomposed of a solid, circular piece concentrically positioned withrespect to the working electrode such that the outer perimeter of thesolid circular piece is circumscribed substantially within the innerperimeter of the annular working electrode. Thus chemical signal thatpasses with the electrolyte flow and through the plane of the mask issubstantially only that chemical signal that is transported from thechemical signal source in a direction that is substantiallyperpendicular to the working electrode catalytic face.

In another embodiment, the mask is attached to a surface of a hydrogelpatch, and the mask and hydrogel patch are provided as a single unit.

In another embodiment, the mask is an integral part of the housing forthe sensor portion of a device for monitoring the chemical signal.

In another embodiment, the mask is independent of any portion of thedevice with which it is to be used, i.e., the mask is not bound toanother component but merely placed, by the user, in contact with theelectrolyte containing material prior to use.

An object of the invention is to provide a means that can be used withvirtually any surface-contacting working electrode, and can enhance theperformance of the electrode and the accuracy of measurements from theworking electrode.

Another object of the invention is to provide a means for accurately andconsistently measuring the amount of a chemical signal present in asample by minimizing the error created by chemical signal which moves tothe electrode with a radial vector component.

Another object of the invention is to provide a means for quickly,accurately, and continually measuring a chemical signal transportedthrough an electrolyte containing ion conducting material, e.g., ahydrogel. By using the mask of the invention with a working electrode asdescribed herein, measurement of the chemical signal transported throughthe material in a path perpendicular to the electrode is achieved withina matter of seconds to minutes.

An object of the invention is to provide a disposable assembly whichmakes it possible to proportionally measure a chemical signal byconversion into an electrical signal, where the electrical signal can bemeasured and accurately correlated with the amount of chemical signalpresent in a given source (e.g., the amount of chemical signal presentin and/or below a section of skin, or in a hydrogel patch in contactwith the working electrode).

An advantage of the invention is that use of the mask with a workingelectrode and hydrogel allows for measurement of very small amounts ofan electrochemical signal. For example, the mask of the invention can beused in conjunction with a working electrode, electroosmotic electrodeand hydrogel system for monitoring glucose levels in a subject. Anelectroosmotic electrode (e.g., reverse iontophoresis electrode) can beused to electrically draw glucose into the hydrogel. Glucose oxidase(GOD) contained in the hydrogel catalyzes the conversion of glucose togenerate a reaction product (hydrogen peroxide) which can beproportionally converted to an electrical signal. The electroosmoticelectrode is switched off and the working electrode of the invention isturned on. The working electrode catalyzes the resulting chemical signalinto an electrical signal which is correlated to the amount of chemicalsignal. This system allows for the continuous and accurate measurementof an inflow of a very small amount of glucose (e.g., glucoseconcentrations 10, 500, or 1,000 or more times less than theconcentration of glucose in blood).

Another advantage is that the mask is easily and economically producedand is disposable.

A feature of the mask and the device used therewith is that it is flat(e.g., a disk with substantially planar surfaces), thin (e.g., 0.5 to 10mils), impermeable to chemical signal flow with theelectrode/mask/hydrogel assembly having a surface area on each face inthe range of about 0.5 cm² to 10 cm².

A feature of the mask is that where the mask includes an opening, theopening has substantially the same dimensions or smaller as the workingelectrode i.e., the outer perimeter of the opening is circumscribedwithin the outer perimeter of the catalytic surface of the workingelectrode.

These and other objects, advantages and features of the presentinvention will become apparent to those persons skilled in the art uponreading the details of the composition, components and size of theinvention as set forth below reference being made to the accompanyingdrawings forming a part hereof wherein like numbers refer to likecomponents throughout.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an overhead schematic view of a disc or donut shapedembodiment of the mask of the invention.

FIGS. 2A and 2B are cross-sectional views of embodiments of anelectroosmotic electrode/working electrode/hydrogel patch assembly witha mask according to the invention.

FIG. 3 is a cross-sectional view of an electroosmotic electrode/sensingelectrode/hydrogel patch assembly without a mask according to theinvention.

FIG. 4 is a schematic representation of the reaction which glucoseoxidase (GOD) catalyzes to produce gluconic acid and hydrogen peroxide;hydrogen peroxide is then catalyzed at the working electrode intomolecular oxygen, 2 hydrogen ions, and 2 electrons, the latter of whichgenerates an electrical current.

FIG. 5 is a cross-sectional schematic view of a mask of the inventionprovided below a hydrogel patch.

FIG. 6 is an overhead schematic view of a sensor housing containingelectroosmotic and working electrodes and a mask.

FIG. 7 is a graph showing the measured electrical current at the workingelectrode in the absence of the mask for different intervals as afunction of time.

FIG. 8 is a graph showing the measured electrical current at the workingelectrode in the presence of the mask for different intervals as afunction of time.

FIG. 9 is a graph showing a comparison of the measured electricalcurrent at the working electrode either with the mask or without themask as a function of interval number.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Before the mask of the present invention and assembly comprising such isdescribed and disclosed it is to be understood that this invention isnot limited to the particular components or composition described assuch may, of course, vary. It is also to be understood that theterminology used herein is for the purpose of describing particularembodiments only, and is not intended to be limiting since the scope ofthe present invention will be limited only by the appended claims.

It must be noted that as used in this specification and the appendedclaims, the singular forms "a", "an" and "the" include plural referentsunless the context clearly dictates otherwise. Thus, for example,reference to "a molecule" includes a plurality of molecules anddifferent types of molecules.

Unless defined otherwise all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although any materials ormethods similar or equivalent to those described herein can be used inthe practice or testing of the present invention, the preferred methodsand materials are now described. All publications mentioned herein areincorporated herein by reference for the purpose of describing anddisclosing the particular information for which the publication wascited in connection with.

Definitions

The term "mask," "impermeable mask," or "mask of the invention" means athin (less than 50 mils, preferably 0.5 mil to 5 mils in thickness),substantially flat piece of material that, when positioned within thetransport path of chemical signal moving toward a working electrode,reduces or prevents transport of chemical signal in a radial directionfrom the chemical signal source. The mask can be positioned on a face ofthe ionically conductive material, or can be positioned at any positionwithin the ionically conductive material (e.g., such that the mask iscontacted by material on each of its planar surfaces). In one exemplaryconfiguration, the mask has an opening, which opening is substantiallythe same shape and size (e.g., smaller than or equal to) that of theworking electrode. Thus, the outer perimeter of the opening iscircumscribed substantially within the outer perimeter of the catalyticsurface of the working electrode. When the opening is circular, thediameter is equal to or less than the diameter of the circular catalyticsurface of a working electrode with which the mask is to used. In analternative exemplary configuration, the mask is a solid piece ofmaterial (i.e., does not have an opening), and is used in conjunctionwith, for example, an annular working electrode. This type of mask isconcentrically positioned with respect to the working electrode, so thatchemical signal does not enter the region substantially concentric tothe annular working electrode. The mask is composed of a material thatis substantially impermeable to the flow of chemical signal that is tobe detected. The mask and/or the mask opening are of a size sufficientto allow a detectable amount of chemical signal to reach the workingelectrode, while reducing or preventing entry of chemical signal intothe electrolyte flow path that has a potential to be transported (eg.,by diffusion) in a radial direction toward an edge of the workingelectrode. Thus, the mask substantially eliminates "edge effect" flow,i.e., the chemical signal impermeable mask area prevents chemical signalfrom contacting the electrode unless the signal flows substantiallyperpendicular to the surface of the working electrode.

The term "working electrode" means an electrode that detects a chemicalsignal by catalyzing the conversion of a chemical compound into anelectrical signal (e.g., conversion of hydrogen peroxide into 2electrons, molecular oxygen, and 2 hydrogen ions).

The term "catalytic surface" or "catalytic face" means the surface ofthe working electrode that: 1) is in contact with the surface of anionically conductive material which comprises an electrolyte and allowsfor the flow of chemical signal; 2) is composed of a catalytic material(e.g., carbon, platinum, palladium, nobel metal, or nickel and/or oxidesand dioxides of any of these); and 3) catalyzes the conversion of thechemical signal into an electrical signal (i.e., an electrical current)that is monitored and correlated with an amount of chemical signalpresent at the electrode.

"Chemical signal," "electrochemical signal," or "electrochemicallyactive compound" means the chemical compound that is ultimatelyconverted to an electrical signal and measured by the working electrodein conjunction with a monitoring device. Chemical signal which movestoward the working electrode at an angle, i.e., includes a radial vectorcomponent, is blocked by the mask. "Chemical signals" can be: 1)directly converted into an electrical signal by chemical reaction at thecatalytic face of the electrode; or 2) indirectly converted into anelectrical signal by the action of one or more catalysts. For example,the chemical signal glucose is indirectly converted into an electricalsignal by reactions driven by two catalysts. A first catalyst, theenzyme glucose oxidase (GOD), converts glucose into gluconic acid andhydrogen peroxide. Hydrogen peroxide is then converted to an electricalsignal by a second catalyst which second catalyst is the catalyticmaterial (e.g., metal or metal oxide on the catalytic face of theworking electrode.

"Ionically conductive material" means a material that provides ionicconductivity, and through which electrochemically active species can betransported (e.g., by diffusion). The ionically conductive material canbe, for example, a solid, liquid, or semi-solid (e.g., in the form of agel) material that contains an electrolyte, which can be composedprimarily of water and ions (e.g., sodium chloride). Generally, thematerial comprises water at 50% or more by weight of the total materialweight. The material can be in the form of a gel, a sponge or pad (e.g.,soaked with an electrolytic solution), or any other material that cancontain an electrolyte and allow passage of electrochemically activespecies, especially the chemical signal of interest, through it. Anexemplary ionically conductive material in the form of a hydrogel isdescribed in copending U.S. application Ser. No. 08/501,664, filed Jul.12, 1995, incorporated herein by reference.

A "chemical signal target area" is an area on a surface of an tonicallyconductive material toward which chemical signal transport is desired.The chemical signal target area is generally an area of the ionicallyconductive material that, during chemical signal monitoring, is incontact with a chemical signal sensing means (e.g., a catalytic face ofa working electrode), and is of the same size and shape as the portionof the chemical signal sensing means in contact with the ionicallyconductive material surface (e.g., the same size and shape as thecatalytic face of the working electrode). For example, where thechemical sensing means to be used with the ionically conductive materialis a circular working electrode, the chemical signal target area is acircular area of the ionically conductive material face that contactsthe catalytic surface of the circular working electrode during chemicalsignal monitoring. In another example, where the chemical sensing meansto be used with the ionically conductive material is an annular workingelectrode, the chemical signal target area is an annular area of theionically conductive material face that contacts the catalytic surfaceof the circular working electrode during chemical signal monitoring.

Mask (General)

The invention must provide some basic characteristics in order to beuseful for its intended purpose, which is to inhibit contact between aworking electrode and radially inward transported chemical signal,particularly the form of the chemical signal that can be catalyzed intoan electrical signal at the catalytic surface of the electrode (e.g.,hydrogen peroxide that results from conversion of the chemical signalglucose).

For example, the mask of the invention can be used in connection withany metabolite monitoring device, where the device contains a workingelectrode that detects a chemical signal that is transported from onearea (e.g., the skin and tissues below the skin) through an ionconducting material (e.g., a hydrogel) to the electrode surface.Examples of such devices include those described in PCT application Ser.No. PCT/GB93/00982 (incorporated herein by reference). Further exemplarydevices, hydrogels, and additional components for use with the presentinvention are described in copending U.S. application Ser. No.08/501,664, filed Jul. 12, 1995; and in copending U.S. applicationentitled "Electrode," filed on Sep. 11, 1995 as attorney docket no.07498/003001; each of which applications are herein incorporated byreference in their entirety and which applications disclose inventionswhich were invented under an obligation to assign rights to the sameentity to which the rights in the present invention were invented underan obligation to assign.

An exemplary ionically conductive material suitable for use with theinvention is a hydrogel composed of a hydrophilic compound, water, and asalt. The hydrophilic compound forms a gel in the presence of water, andis generally present in the gel in an amount of about 4% or more byweight based on the total gel weight. The gel contains water in anamount of about 95% or less based on the weight of the hydrogel. Thesalt can be any salt that ionizes readily in water and facilitateselectric conductivity through the gel, preferably a chloride containingsalt (e.g., NaCl, KCl, etc.).

Regardless of the composition of the ionically conductive material, oneface of the material has a chemical signal target area. The target areais the area on a face of the material toward which chemical signaltransport is desired, e.g., the area of the material face that will bein contact with the catalytic face of a working electrode duringchemical signal sensing. Preferably, the target area of the ionicallyconductive material is used with a working electrode that has acatalytic face having approximately the same shape and size as thetarget area (e.g., circular, annular, etc.). During monitoring, the maskis positioned on a second tonically conductive material face oppositethe first material face having the target area, such that chemicalsignal that diffuses from the chemical signal source, through a plane ofthe mask, through the ionically conductive material, and toward thechemical signal target area is substantially only that chemical signalthat is transported in a direction substantially perpendicular to thechemical signal target area.

An exemplary monitoring device that can be used in connection with themask of the invention is generally composed of: 1) a hydrogel patch, oneface of which is contacted with a source of biologically importantmolecules such as the skin of a mammalian subject; 2) an electroosmoticelectrode which is positioned on the face of the hydrogel patch oppositethe face in contact with the mammalian subject's skin; 3) a workingelectrode having a catalytic material on at least its catalytic face,the catalytic face of the electrode being that face in contact with thesame face of the hydrogel as the electroosmotic electrode; 4) a meansfor generating an electrical current through the electroosmoticelectrode, the electrical current serving to electrically draw moleculesthrough the mammalian subject's skin, into the hydrogel patch, andtoward the catalytic face of the working electrode; and 5) a monitoringmeans for monitoring electrical current generated at the catalytic faceof the working electrode. Alternatively, the chemical signal can enterthe hydrogel by passive diffusion, i.e., the assembly can be usedwithout an electroosmotic electrode.

Such a monitoring device can be used to monitor levels of ametabolically important compound in, for example, the bloodstream of amammalian subject (e.g., a human subject). As used herein, the metaboliccompound in this example is termed the "chemical signal." For example,the metabolic compound (and chemical signal) can be glucose. Thatchemical signal is converted to a useful chemical signal and thenconverted to an electrical signal as shown in FIG. 4. The electroosmoticelectrodes are used to electrically draw glucose molecules through themammalian subject's skin, into the hydrogel, and toward the catalyticface of the working electrode. The hydrogel contains the enzyme glucoseoxidase (GOD), which converts the glucose into gluconic acid andhydrogen peroxide. The hydrogen peroxide is then converted intomolecular oxygen, 2 hydrogen ions, and 2 electrons, the latter of whichgenerates an electrical current in the working electrode (see FIG. 4).The electrical current is measured by the attached monitoring device,and correlated with the amount of glucose present in the subject'sbloodstream.

An assembly of the invention comprised of an electrode and maskpositioned on either side of a hydrogel is used with a monitoring deviceas described above by positioning the mask between mammalian subject'sskin and the face of the hydrogel in contact with the subject's skin,such that chemical signal that diffuses from the subject's skin and pastthe plane of the mask is only that chemical signal that is transportedin a path substantially perpendicular to the catalytic face of theworking electrode. It is important that the mask does not completelyocclude contact of the ionically conductive material (e.g., thehydrogel) with the chemical signal source (e.g., the subject's skin).

An exemplary assembly of the invention is shown in FIG. 2A, where theworking electrode 4 and mask 1 are circular, and the mask has an opening2 that is positioned so that it is directly beneath the workingelectrode 4 on the opposite face of the gel 3. Because the mask isimpermeable to the chemical signal (e.g., glucose), chemical signal iselectrically drawn via a substantially perpendicular path only throughthe opening in the mask. An additional exemplary assembly of theinvention is shown in FIG. 2B, where the working electrode is annular(circular with a circular opening in the center), and the mask 1 is asolid, circular piece positioned concentric to the working electrodesuch that the outer perimeter of the mask 1 is substantiallycircumscribed within the inner perimeter of the annular workingelectrode 4. In this embodiment, the annular working electrode extendsfrom approximately the outer perimeter of the mask to the outerperimeter of the ionically conductive material (e.g., hydrogel) used inconjunction with the mask 1 and working electrode 4. For example, wherethe radius of the a circular hydrogel is 0.95 cm, the radius of the maskcan be about 0.5 cm and the width of the working electrode is about 0.45cm.

The position of the mask, and the inhibition of the entry of glucoseinto gel areas other than that directly beneath the working electrodeminimizes the radial component of chemical signal transport. Reductionof radial transport of the chemical signal toward the working electrodereduces accumulation of such radially transported compound at theperiphery of the electrode, thereby reducing the edge effects associatedwith this phenomenon. It is recognized that the mask can allow for asmall amount of radial chemical signal transport from the chemicalsignal source toward the working electrode where, for example, the errorin measured electrical current associated with electrochemicalconversion of the radially transported chemical signal is of a magnitudethat does not significantly affect the accuracy of the measurement ofthe amount of chemical signal (e.g., the concentration of chemicalsignal in a subject's bloodstream). Thus, for example, where the maskhas an opening, the opening can be slightly larger than the diameter ofthe working electrode used in conjunction with the mask.

The (1) size or geometric surface area of the working electrode, (2)thickness of the gel, (3) size of the opening in the mask, and (4) widthof the mask surrounding the opening are all interrelated to each other.For example, when the thickness of the gel is increased the size of theopening must be decreased to obtain the same degree of elimination ofradially transported chemical signal. The smaller the opening in themask the greater the ability to block radial transport of chemicalsignal. Although it is desirable to decrease radial transport of thechemical signal, it is also desirable to maximize the chemical signalreceived and the chemical signal is decreased by a smaller opening inthe mask.

For reasons that may relate to factors such as the build up of undesiredmaterials, components such as the hydrogel, mask and the electrodes mustbe easily replaceable by a patient in a convenient manner. Accordingly,an assembly of these components must have some structural integrity, andprovide for the detection of the chemical signal of interest. In thatthe device is preferably small (e.g., hand held, e.g., the size of awatch to be worn on the wrist of a patient), it is necessary that theassembly of components be particularly thin. The mask generally has athickness of about 0.5 to 10 mils (1 mil equals one thousandth of aninch) and the hydrogel has a thickness in the range of about 5 mils to60 mils, generally about 10 mils to 60 mils, normally about 600 microns(about 24 mils).

In order to accurately measure the amount of a chemical signal (e.g.,the amount of hydrogen peroxide generated by GOD catalysis of glucose)and be sufficiently large to be manipulated, the device cannot be toothin and cannot be too small. The overall surface area of the hydrogelon a single surface should be in the range of about 0.25 cm² to about 10cm², preferably about 0.50 cm² to 5 cm². The electrodes of the entiremonitoring device, which include both electroosmotic and workingelectrodes, must have a total surface area that is less than that of thehydrogel patch. In general, the surface area of a mask (the area of themask, and the opening where applicable) suitable for use in themonitoring device ranges from about 0.1 cm² to about 6 cm², preferablyabout 0.25 cm² to 2.0 cm², more preferably about 1.0 cm².

Basic Structure

FIG. 1 is an overhead schematic view of an exemplary mask of theinvention. The mask may be any configuration but is preferably donutshaped as per FIG. 1, with an outer perimeter that is equal to or largerthan that of the working electrode and/or is substantially the same asthe hydrogel patch used in conjunction with the mask. The mask openingis generally equal in size to about 50% of the area of the workingelectrode ±20%. In general, the mask opening constitutes an area that isin the range of 1% to 90% of the area encompassed by the mask plus theopening. The mask 1 is disc-shaped, and has a diameter equal to or lessthan the diameter of the hydrogel patch used in conjunction with themask, the diameter being in the general range of about 0.5 cm to 3.0 cm,generally about 1.9 cm. In general, the range of the surface area of thehydrogel patch used in conjunction with the mask is from about 0.5 cm²to about 10 cm², preferably in the range of about 1 cm² to about 5 cm².The mask 1 defines an opening 2 positioned substantially in the centerof the mask 1. The diameter of opening 2 is less than or equal to thediameter of the catalytic surface of the working electrode that is to beused in conjunction with the mask, generally in the range of about 0.4cm. Normally, the mask opening constitutes an area that is about 5/8±15%of the total area encompassed by the catalytic face of the workingelectrode, equal to, or slightly larger than the catalytic face of theworking electrode (e.g., 100.5% to 105% of the catalytic surface area).

Alternatively, the mask can be a composed of a solid, circular piece foruse with, for example, an annular working electrode. The solid, circularmask is concentrically positioned with respect to an annular workingelectrode such that the outer perimeter of the solid circular piece iscircumscribed substantially within the inner perimeter of the annularworking electrode. Thus chemical signal that diffuses from the chemicalsignal source and through the mask(s) is substantially only thatchemical signal that diffuses from the chemical signal source in adirection that is substantially perpendicular to the plane of the mask,and thus, substantially perpendicular to the annular working electrodecatalytic face.

The mask is preferably thin, generally having a thickness in the rangeof about 0.01 mil to 10 mils, normally about 0.5 mil to 5 mils (1 milequals one-thousandth of an inch). The working electrode used inconjunction with the mask of the invention generally has a geometricsurface about 5% to 90%, preferably about 10% to 80% of the geometricsurface of the hydrogel.

The mask is composed of a material that is substantially impermeable tothe chemical signal to be detected (e.g., glucose), and can be permeableto substances other than the chemical signal of interest. By"substantially impermeable" is meant that the mask material reduces oreliminates chemical signal transport (e.g., by diffusion). The mask canallow for a low level of chemical signal transport, with the provisothat chemical signal that passes through the material of the mask doesnot cause significant edge effects at the working electrode use inconjunction with the mask. Examples of materials that can be used toform the impermeable mask include mylar, polyethylene, nylon and variousother synthetic polymeric material. The mask can be composed of a singlematerial, or can be composed of two or more materials (e.g., the mask iscomposed of multiple layers of the same or different materials) to forma chemical signal-impermeable composition.

In general, the size of the mask (i.e., diameter, surface area,thickness, etc.), the geometry of the mask (e.g., circular, oval,annular, polygonal, etc.), the size (e.g., diameter, surface area, etc.)and/or geometry (e.g., annular, circular, oval, polygonal) of a maskopening through which the chemical signal is to be detected,compositions of the mask (e.g., type and number of materials, number oflayers, chemical signal to which the mask is permeable), the number ofmask used in an assembly of the invention (i.e., the number and positionof the masks in the electrolyte flow path between the catalytic surfaceof the working electrode and the chemical signal source) and othercharacteristics of the mask will vary according to a variety of factorssuch as, for example, the diameter of the hydrogel patch, the diameterof the working electrode, the diameter of the electroosmotic/workingelectrode assembly, the chemical signal to be detected, thecharacteristics of the chemical signal's path of transport (e.g., thediffusion characteristics of the chemical signal), and the geometry andsize of the monitoring device.

Methods for making the mask include die cutting and stamping accordingto methods well known in the art. Most preferably, the mask ismanufactured in a manner that is the most economical withoutcompromising performance of the mask (e.g, the impermeability of themask to the chemical signal of interest, the ability to manipulate themask by hand without breaking or otherwise compromising itsoperability). The mask may have an adhesive including a pressuresensitive adhesive coated on one or both surfaces. Further, the mask maybe coated with a material which absorbs one or more compounds or ionsflowing in the hydrogel.

Configurations

The mask can be supplied in several different configurations. Examplesof these configurations include: 1) the mask supplied in connection witha hydrogel patch; 2) the mask supplied as an integral component of amonitoring device; or 3) the mask supplied as an independent component.

FIG. 5 illustrates how the mask of the invention can be supplied with ahydrogel patch as a hydrogel/mask assembly 12. The mask 1 is positionedon one face of the gel 3. The mask can be attached to the gel 3 by anysuitable chemical means (e.g., adhesive) that do not affect theimpermeability of the mask to the chemical signal of interest or theconductivity of the gel for electrically-induced movement of thechemical signal through the mask opening and into and through thehydrogel. Release liner components 9 and 10 are positioned on oppositesurfaces of the assembly 12 to provide improved handleability of theassembly 12 in that the assembly 12 may be slightly fragile (e.g., maytear during shipping or repeated handling) and/or wet and sticky. Therelease liner 10 may include a perforated cut (e.g., an S-shaped cut) ormay include two portions 11 and 13 that overlap one another to alloweasy removal of the release liner 10. Prior to use, the release liners 9and 10 are removed from the assembly 12, and the assembly 12 positionedin the sensor housing of a monitoring device so that the mask will be incontact with the subject's skin, and the hydrogel will be in contactwith the electroosmotic and working electrodes.

In another embodiment, the mask is an integral component of the sensorhousing of a monitoring device. An example of a sensor housing of amonitoring device is illustrated in FIG. 6. The sensor housing 16 of themonitoring device includes a top portion 15 containing electroosmotic 5and working 4 electrodes, and a bottom portion 14 defining an opening17, the opening having a diameter at least slightly less than that ofthe mask 1 so that the mask fits tightly in the recess 19. The topportion 15 and the bottom portion 14 can be connected by a hinge 18 thatpermits opening and closing of the sensor housing. The mask 1 is eitherpermanently or removably fitted over this sensor housing opening 17. Theedges of the sensor housing opening 17 can define a recess 19 so as toeasily receive the mask 1 and seat the mask 1 within the recess 19. Themask can be secured into position in the bottom portion 14 of the sensorhousing 16 by any suitable chemical means (e.g., adhesive) or physicalmeans (e.g., physically attaching the mask to the opening by melting theedges of the mask 1 edges to the edges of the opening 17), provides thatthe operability of the mask, the hydrogel, the sensor housing, and/orthe monitoring device are not significantly affected.

The entire assembly is used by inserting a hydrogel patch (as per thegel 3 of FIG. 5) over the mask 1 in the bottom portion 14, and bringingthe top portion 15 into position over the bottom portion 14 so that theelectroosmotic electrode 5 and working electrodes 4 contact the centralportion of the hydrogel. The top portion 15 and the bottom portion 14can be held together by interconnecting portions of a securing means 19(e.g., a latch) which can be closed and opened repeatedly, preferablyfor the life of the sensor housing. The bottom portion 14 is thenpositioned on the subject's skin so that the hydrogel contained withinthe bottom portion 14 is in contact with the skin through opening 2.When properly aligned, the opening 2 in the mask 1 is positioned beneaththe approximate center of the catalytic face 6 of the working electrode4, so that chemical signal that is transported axially through thehydrogel accessible through the mask opening 2 and will come in contactwith the central portion of the catalytic face 6 of the workingelectrode 4.

In another embodiment, the mask is supplied as an independent component,e.g. for insertion into a sensor housing as exemplified in FIG. 6. Themask is inserted in the device prior to use as described above and inFIG. 6, the hydrogel inserted within the bottom portion of the sensorhousing and on top of the mask, and the device assembled as describedabove.

Regardless of the embodiment used, all of the masks of the invention: 1)are impermeable to the chemical signal to be detected; 2) have adiameter that is at least the same or greater than the diameter of thehydrogel patch used in conjunction with the mask; and either 3) areconfigured for use with a working electrode so that when positioned inthe path of electrolyte flow from the chemical signal source,substantially only chemical signal that flows from the source in adirection substantially perpendicular to the working electrode isallowed to enter the electrolyte flow path.

The mask is generally used in conjunction with an electroosmoticelectrode (e.g., an iontophoresis or reverse iontophoresis electrode).An electroosmotic electrode suitable for use with the invention isdescribed in copending U.S. application Ser. No. 08/2265,844, filed Jun.24, 1995 (which application is incorporated herein by reference in itsentirety, and which discloses an invention invented under an obligationto assign to the same entity as that to which the rights in the presentapplication are assigned).

The electroosmotic electrode is used to create an electrical field whichtransports material such as ions and non-polar molecules from one area(e.g., skin, blood and flesh) to the area of the working electrode. Itis important the electroosmotic electrode and the working electrode beused alternately (i.e., current is present in the electroosmoticelectrode or the electrical current generated at the working electrodeis measured--not both at once).

Working electrodes suitable for use with the invention include anyelectrode having a catalytic surface for detection of a chemical signal.An example of a suitable working electrode is described in copendingU.S. application entitled "Electrode," filed on Sep. 11, 1995 asattorney docket no. 07498/003001, incorporated herein by reference. Astandard bipotentiostat circuit can be used to bias the working andscavenging electrodes independently versus the reference electrode.

Based on the description above and in the figures, it will be recognizedthat the working electrode of the invention can be configured in avariety of different forms, and from a variety of different materials.The mask will change with the working electrode so as to maintaincertain defined mechanical, electrical, chemical and transport (e.g.,diffusion) characteristics.

Mechanically the mask will have sufficient structural integrity suchthat it can be readily handled by human fingers without significanthandling difficulties or significantly compromising the performance ofthe mask. Preferably, the mask will be somewhat flexible so that it canbend at least slightly during handling without creasing, breaking, orbeing otherwise compromised in, for example, its impermeability to thechemical signal of interest. The relative mechanical requirements of themask may vary with the particular mask embodiment. For example, wherethe mask is an integral part of the sensor housing, it may be desirableto design the mask so that it can be separated from the patch withoutsignificantly tearing the patch, or adhering to the patch in a mannerthat makes it difficult to completely remove all patch material from theface of the mask.

The mask must maintain its impermeability to the chemical signal ofinterest. Preferably, the mask will optimally function at a pH which isrelatively close to that from which the chemical signal is withdrawn(e.g, human skin (about 7)) and at least within a range of from about pH4 to pH 9.

Utility

The present invention is useful in connection with the detection ofbiologically significant molecules such as glucose which is movedthrough human skin using a technique known as electroosmosis. The basicconcept of moving a molecule such as a glucose through human skin isdisclosed within U.S. Pat. No. 5,362,307, issued Nov. 8, 1994 and U.S.Pat. No. 5,279,543, issued Jan. 18, 1994 which patents are incorporatedherein by reference for disclosing the basic concept of moving moleculessuch as glucose through human skin by means of electroosmosis. Theconcept of converting the very small amounts of molecules such asglucose which can be extracted through the skin in order to create acurrent by use of glucose oxidase is disclosed within earlier filedapplication Ser. No. 08/265,084, filed Jun. 24, 1994 and applicationSer. No. 08/373,931, filed Jan. 10, 1995; hydrogel patches and workingelectrodes suitable for use with the present invention are disclosedwithin copending U.S. application Ser. No. 08/501,664, filed Jul. 12,1995; and copending U.S. application entitled "Electrode," filed on Sep.11, 1995 as attorney docket no. 07498/003001; each of which applicationsare incorporated herein by reference in their entirety and whichapplications disclose inventions which were invented under an obligationto assign rights to the same entity to which the rights in the presentinvention were invented under an obligation to assign.

FIG. 2A illustrates how an exemplary mask of the invention is used inconjunction with a hydrogel/electroosmotic electrode/working electrodesystem, such as that used in a metabolite monitoring device (e.g., aglucose monitoring device). The mask 1 is positioned on a face of thegel 3 with the opening 2 substantially in the center of the gel 3. Aworking electrode 4 and electroosmosis electrode 5 are positioned on theface of the gel 3 opposing the mask 1. The catalytic surface 6 of theworking electrode 4 is positioned on the gel 3 so that the workingelectrode 4 is directly opposite the opening 2 of the mask 1. The faceof the gel 3 attached to the mask 1 is placed on the surface 7 throughwhich the chemical signal is to be diffused (e.g., mammalian skin, e.g.,human skin).

During use in monitoring levels of a chemical signal of interest (e.g.,glucose), an electrical current is sent through the electroosmoticelectrode, thereby drawing molecules through the patient's skin and intothe hydrogel patch. The mask permits entry of the chemical signal intothe gel only at the opening 2, thus reducing the amount of chemicalsignal that is radially transported into the patch, as well as theamount of chemical signal that is capable of being transported radiallytoward the working electrode. The mask creates a column-like flowthrough the gel to the working electrode and substantially prevents anymaterial from flowing to the electrode if that material includes aradial vector as a component of its movement, i.e., the material mustmove axially or perpendicular to the working electrode. The chemicalsignal permitted into the patch by entry through the opening in the maskis transported in a substantially axial direction toward the catalyticsurface 6 of the working electrode 4, where it is converted to anelectrical signal. Alternatively, the chemical signal is converted intoan intermediate compound by a component in the gel 3. The intermediatecompound in turn is transported to the catalytic surface 6 of theworking electrode 4, where it is converted into an electrical signal.The electrical signal is detected by switching off the electroosmoticelectrode, and monitoring the electrical current generated at theworking electrode.

The use of the mask and advantages associated therewith are furtherillustrated by comparing the flow of glucose in a monitoring systemeither with (FIGS. 2A and 2B) or without (FIG. 3) the mask of theinvention. FIG. 3 illustrates an electroosmotic electrode/workingelectrode/hydrogel patch assembly (without a mask of the invention) formonitoring glucose levels in a mammalian subject (e.g., a humansubject). As described above, the electroosmotic electrodes (e.g.,iontophoresis electrodes) 5 are activated to electrically draw glucose 8through the subject's skin 7 and into the hydrogel 3. The iontophoresiselectrode 5 is used to electrically draw glucose 8 through the subject'sskin 7 and into the hydrogel 3. Glucose 8 is permitted to enter the gel3 over the entire face of the gel 3 in contact with the subject's skin7. As a result, glucose is present throughout the entire gel 3, ratherthan in a region substantially perpendicular to the catalytic face 6 ofthe working electrode 4. The gel 3 contains the enzyme glucose oxidase(GOD), which converts the glucose to hydrogen peroxide and gluconicacid. The conversion of glucose to hydrogen peroxide by GOD isillustrated schematically in FIG. 3. The hydrogen peroxide istransported (e.g., by diffusion) toward the catalytic face 6 of theworking electrode 4, where it is converted into molecular oxygen, 2hydrogen ions, and 2 electrons, the latter of which provides anelectrical signal.

Because glucose is present throughout the entire gel 3, the hydrogenperoxide resulting from enzymatic conversion of glucose is also presentthroughout the entire gel 3. Because the surface area of the gel isgreater than that of the working electrode, uncatalyzed hydrogenperoxide accumulates at the working electrode 4 periphery due to radialtransport of the compound toward the catalytic surface 6. Accumulationof peroxide at the working electrode periphery produces a variablehydrogen peroxide flux (i.e., the amount of peroxide present over theworking electrode at a given time is not directly correlated with theactual peroxide flux through the hydrogel), and thus produces a flux orerror in the measured electrical current at the working electrode.

In contrast, and as illustrated in FIGS. 2A and 2B, the mask 1 of theinvention permits entry of glucose 8 only at the opening 2 (in FIG. 2A)or the non-mask contacting portion of the gel 3 (as in FIGS. 2A and 2B).The opening and/or non-mask contacting gel surface is directly oppositethe catalytic surface 6 of the working electrode 4. The glucose 8 isconverted into hydrogen peroxide and gluconic acid by GOD, which iscontained in the gel 3. The hydrogen peroxide produced is generallypositioned within the gel in a region that is beneath and substantiallyperpendicular to the catalytic face 6 of the working electrode 4. Thus,the radial transport component of hydrogen peroxide illustrated in FIG.3 is eliminated, and an increased flux or error in current measured atthe working electrode 4 periphery does not occur.

The composition, size and thickness of the mask and other components canbe varied and such variance can affect the time over which thecomponents can be used. For example, the hydrogel patches may beconnected to the mask and are generally designed to provide utility overa period of about 24 hours. After that time some deterioration incharacteristics, sensitivity, and accuracy of the measurements from theelectrode can be expected (e.g., due to reduced effectiveness of anenzyme in the hydrogel). Due to other problems the working electrode andhydrogel patch, preferably the entire device, should be replaced. Theinvention contemplates components, assemblies and devices which are usedover a shorter period of time e.g., 8 to 12 hours or a longer period oftime e.g., 1 to 30 days.

In its broader sense, a mask of the invention can be used to carry out amethod which comprises extracting any biomedically significant substancethrough the skin of a human patient and reacting that substance withanother substance or substances (which reaction is greatly acceleratedby the use of an enzyme e.g., 10 to 100 times or more as fast) to form aproduct which is detectable electrochemically by the production of asignal which signal is generated proportionally based on the amount of abiologically important or biomedically significant substance drawn intothe patch. As indicated in the above-cited patents the ability towithdraw biochemically significant substances such as glucose throughskin has been established (see U.S. Pat. Nos. 5,362,307 and 5,279,543).However, the amount of compound withdrawn is often so small that it isnot possible to make meaningful use of such methodology in that thewithdrawn material cannot be precisely measured and related to anystandard.

Moreover, conventional hydrogel/working electrode assemblies areseverely compromised in their ability to accurately, quickly, andcontinuously monitor levels of the chemical signal. As described above,in devices without a mask chemical signal is radially transported towardthe catalytic surface of the working electrode and accumulates at theworking electrode periphery, thus causing the flux or error of chemicalsignal to be greater at the electrode edges than at the electrodecenter, a phenomenon termed "edge effects." The edge effects result invarying electrical signals, and thus varying and inadequate measurementof the flux of the chemical signal. The present invention provides anelectrode that is capable of detecting the electrochemical signal atvery low levels in a manner that allows for direct, accurate correlationbetween the amount of signal generated and the amount of the molecule(e.g., glucose) in the area from which it is moved (e.g., in the humansubject).

The invention is remarkable in that it allows for the noninvasivedetection and measuring of amounts of a biomedically relevant compound,e.g., glucose, at levels that are 1, 2, or even 3 orders of magnitudeless than the concentration of that compound in, for example, blood. Forexample, glucose might be present in blood in a concentration of about 5millimolar. However, the concentration of glucose in a hydrogel patchwhich withdraws glucose through skin as described in the system above ison the order of 2 to 100 micromolar. Micromolar amounts are 3 orders ofmagnitude less than millimolar amounts. The ability to accurately andquickly detect glucose in such small concentrations is attained byconstructing the working electrode with the mask and other componentsdescribed herein.

EXAMPLES

The following examples are put forth so as to provide those of ordinaryskill in the art with a complete disclosure and description of how tomake and use various specific assemblies of the present invention andare not intended to limit the scope of what the inventors regard astheir invention. The data presented in these examples arecomputer-simulated (i.e., the data is generated from a computer model ofthe mask and electrode assembly described herein). The computer model ofthe invention uses the following parameters:

glucose diffusivity: 1.3×10⁻⁶ cm² /sec;

peroxide diffusivity: 1.2×10⁻⁵ cm² /sec;

enzyme rate constant: 735 sec⁻¹ ;

K_(M) for glucose: 1.1×10⁵ nmol/ml;

K_(M) for glucose: 200 nmol/ml;

initial oxygen concentration: 240 nmol/ml;

enzyme loading in gel: 100 U/ml; and

glucose flux: 5 nmol/cm² hr.

Efforts have been made to ensure accuracy with respect to numbers used,(e.g., amounts, particular components, etc.) but some deviations shouldbe accounted for. Unless indicated otherwise, parts are parts by weight,surface area is geometric surface area, temperature is in degreescentigrade, and pressure is at or near atmospheric pressure.

Example 1

(glucose monitoring device--no mask)

The peroxide flux or current error at the surface of a platinum workingelectrode in a glucose monitoring device comprising an iontophoresiselectrode/platinum working electrode/hydrogel assembly (no mask) wassimulated by computer. The computer-based experiments were designed tosimulate the use of the device in vivo (e.g., the manner in which thedevice is used to monitor glucose in a human subject). The computersimulation was based upon a continuous glucose flux into the hydrogel (5nmol/cm² hr), 18 U/ml glucose oxidase loaded into the gel, a gelthickness of 600 microns, and alternate intervals of: 1) iontophoresis(i.e., the iontophoresis electrodes are activated, and glucose moleculesare electrically drawn through the subject's skin and into and throughthe hydrogel patch); and 2) detection of an electrical current at theworking electrode (i.e., the iontophoresis electrode is switched off andthe sensing unit to detect electrical current at the working electrodeis on). The experimental protocol is shown in Table 1.

                  TABLE 1                                                         ______________________________________                                        Experimental Protocol for Computer Simulation                                     Interval                                                                              Interval Length                                                                             Iontophoresis                                                                          Working                                      No. (min) Electrode Electrode                                               ______________________________________                                        1       15            on         off                                            2  5 off on                                                                   3 15 on off                                                                   4  5 off on                                                                   5 15 on off                                                                   6  5 off on                                                                 ______________________________________                                    

This protocol was repeated for a total of 20 intervals. The results ofthe computer model are shown in FIG. 7.

These data indicate that the electrical current measured at the workingelectrode is a function of the interval number, i.e., peroxide flux atthe working electrode increases with increasing interval number. This isa direct result of the accumulation of hydrogen peroxide at theperiphery of the working electrode as a result of radial transport ofhydrogen peroxide within the gel toward the electrode. As a result, thedevice is never able to provide a steady state measurement profile inthe presence of a continuous flow of glucose and hydrogen peroxide.

Example 2

with a mask

The computer model described in Example 1 was repeated with the sameparameters, except that the device included a mask of the inventionpositioned between the subject's skin and the hydrogel. The position ofthe mask allows transport of glucose toward the working electrode onlyin a direction that is substantially axial to the catalytic face of theworking electrode, and thus production of hydrogen peroxide only in aregion of the hydrogel that is directly beneath the working electrode.Therefore, the amount of hydrogen peroxide that is produced at aposition outside the perimeter of the working electrode is essentiallyeliminated.

The results of the computer model, expressed as the measured electricalcurrent as a function of interval number, are shown in FIG. 8. Thesedata indicate that after interval 2, the is independent of intervalnumber. Thus, within only 2 to 4 intervals, the device provides a steadystate profile of the measurement of a continuous flux of hydrogenperoxide.

Example 3

with and without a mask

The data from the computer simulations of measurement of a constantglucose flux (5 nmol/cm² hr) using a glucose monitoring device withoutthe mask (Example 1) and with the mask (Example 2) were analyzed to plotthe electrical current measured at the working electrode after 5 minutesof measurement versus the interval number (FIG. 9). This analysis showsthat in the absence of the mask, there is a strong dependence of themeasured electrical current on the interval number. When the mask of theinvention is included in the device, the profile of the measuredelectrical current is essentially linear, and thus independent ofinterval number (see "with mask" line of FIG. 9).

The instant invention is shown and described herein in what isconsidered to be the most practical, and preferred embodiments. It isrecognized, however, that departures may be made therefrom which arewithin the scope of the invention, and that modifications will occur toone skilled in the art upon reading this disclosure.

What is claimed is:
 1. An assembly for use in a device for monitoring achemical signal which diffuses through the skin of a subject, saidassembly comprising:(a) an ionically conductive material having firstand second opposing faces, wherein said first face comprises a chemicalsignal target area and said second face comprises a skin contact surfacearea; (b) a mask characterized by being substantially impermeable to achemical signal, said mask having first and second opposing faces and anopening extending between said first and second faces, wherein the firstface of the mask is positioned on the skin contact surface of theionically conductive material and the opening in the mask is less thanor substantially equal to said skin contact surface area; and (c) afirst release liner positioned over the first face of the ionicallyconductive material, wherein said first release liner is easily removedprior to use of the assembly.
 2. The assembly of claim 1 furthercomprising a second release liner positioned over the second face of themask, wherein said second release liner is easily removed prior to useof the assembly.
 3. The assembly of claim 1, wherein the mask isattached to the ionically conductive material by chemical means.
 4. Theassembly of claim 3, wherein the mask is attached to the ionicallyconductive material by a chemical adhesive.
 5. The assembly of claim 1,wherein the mask is positioned on the second face such that chemicalsignal transported through a plane of the mask, through the ionicallyconductive material, and toward the chemical signal target area issubstantially only that signal which is transported in a directionsubstantially perpendicular to the chemical signal target area.
 6. Themask of claim 1, wherein the first release liner includes a perforatedcut therein which facilitates removal of the liner from the assembly. 7.The assembly of claim 1, wherein the opening in the mask constitutes anarea which is in the range of 1% to 90% of an area encompassed by theentire mask plus opening.
 8. The assembly of claim 1, wherein theionically conductive material comprises a hydrogel.
 9. The assembly ofclaim 1, wherein the ionically conductive material comprises a chemicalsignal-specific enzyme.
 10. The assembly of claim 9, wherein the enzymeis glucose oxidase and the chemical signal is glucose.
 11. The assemblyof claim 1, wherein the first and second faces of the ionicallyconductive material are coplanar and each has a surface area in a rangeof from about 0.5 to about 10 cm² and the material has a thickness in arange of from about 5 mils to about 50 mils.
 12. The assembly of claim1, wherein the mask has a thickness in a range of from about 0.5 mils toabout 10 mils.
 13. The assembly of claim 1, wherein the mask has anadhesive coated on at least one of said first and second opposing faces.14. The assembly of claim 13, wherein the adhesive is apressure-sensitive adhesive.
 15. The assembly of claim 1, wherein themask is coated with a material which absorbs one or more compounds orions which diffuse through the skin of said subject.
 16. The assembly ofclaim 1, wherein the mask is comprised of a polymeric material.
 17. Theassembly of claim 1, wherein the mask is comprised of two or more layersof the same or different materials to provide a chemicalsignal-impermeable composition.